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Human African trypanosomiasis or sleeping sickness is caused by infection with Trypanosoma brucei gambiense or Trypanosoma brucei rhodesiense parasites, which are transmitted by tsetse flies in sub-Saharan Africa. Control of human African trypanosomiasis is based on case detection, treatment, and vector control. In the past decade, simple rapid diagnostic tests were introduced for gambiense human African trypanosomiasis, facilitating screening in primary health-care facilities. A new oral drug, fexinidazole, became the first-line treatment for gambiense human African trypanosomiasis without severe meningo-encephalitic disease, as well as for rhodesiense human African trypanosomiasis. Medical interventions, in some areas combined with tiny target-based vector control, have substantially reduced human African trypanosomiasis incidence, despite temporary disruptions to health-care systems. The elimination of human African trypanosomiasis as a public health problem has been achieved, and elimination of gambiense human African trypanosomiasis transmission is now targeted for 2030. Improved diagnostics and drugs, continued involvement of populations at risk of disease, health staff, national authorities, and partners and donors all contribute to achieve this goal.

Sleeping sickness, or human African trypanosomiasis, is a potentially life-threatening vectorborne disease of sub-Saharan Africa. Data on a prototype rapid diagnostic test for this condition are presented. To the Editor: Human African trypanosomiasis (HAT), or sleeping sickness, is a life-threatening neglected tropical infection affecting rural populations in sub-Saharan Africa. In West and Central Africa, chronic trypanosomiasis is caused by Trypanosoma brucei gambiense infection. 1 Control of the disease has been facilitated by the use of the card agglutination test for trypanosomiasis, which is particularly suited for large-scale screening of the populations at risk. 2 With the steadily decreasing prevalence of trypanosomiasis, individual rapid diagnostic tests that can be used in primary health centers, that are stable at ambient temperatures, and that are highly specific have become a research priority. . . .

Passive screening of gambiense human African trypanosomiasis (HAT) is based on rapid diagnostic tests (RDT), but sensitivity of the currently commercialised RDTs has hardly been assessed prospectively. In view of the increasing importance of remote testing for HAT, the diagnostic performance of reference laboratory tests also needs further documentation. The study is registered in ClinicalTrials.Gov under identifier NCT03356665. Clinical suspects in 29 health facilities in DR Congo were screened consecutively between October 2017 and December 2020 with 3 HAT RDTs, including HAT Sero K-SeT, an RDT that is nowadays still commercialised. HAT RDT positives were examined parasitologically and their dried blood spots tested in trypanolysis, indirect ELISA/T.b. gambiense, LAMP Trypanosoma brucei Detection Kit and m18S and TgsGp qPCR. Association of clinical signs with HAT, and sensitivity, specificity, and predictive values of the screening and reference laboratory tests were estimated using parasitology as the gold standard. Trypanosomes were detected in 42/3113 study participants. Logistic regression revealed that sleep disruption, enlarged lymph nodes, psychiatric problems, recurrent fever not responding to anti-malarials and motor disorders were significantly associated with HAT (p < 0.05, odds 3.0-10.6). Together, the RDTs detected 253/3113 seropositives. Sensitivity and specificity of HAT Sero K-SeT were respectively 100% (42/42; 95% CI 91.6-100%) and 93.9% (2882/3071; 95% CI 92.9-94.6%). Specificities of the reference laboratory tests were ≥ 91.6%, except for LAMP. Sensitivity of ELISA/T.b. gambiense and trypanolysis were 93.9% (31/33; 95% CI 80.4-98.9) and 84.9% (28/33; 95% CI 69.1-93.4), and were ≤ 63.6% for LAMP, m18S and TgsGp qPCR. Compared to the WHO's target product profiles for gambiense HAT RDTs, the HAT Sero K-SeT RDT had ideal sensitivity but its specificity was on the borderline of minimally acceptable. Sub-optimal sensitivities of trypanolysis and to a lesser extent, indirect ELISA/T.b. gambiense when applied on DBS, were confirmed. Molecular tests for remote testing need to be improved and evaluated further.

Background Little is known about the diagnostic performance of rapid diagnostic tests (RDTs) for passive screening of human African trypanosomiasis (HAT) in Côte d'Ivoire. We determined HAT prevalence among clinical suspects, identified clinical symptoms and signs associated with HAT RDT positivity, and assessed the diagnostic tests' specificity, positive predictive value and agreement. Methods Clinical suspects were screened with SD Bioline HAT, HAT Sero-K-Set and rHAT Sero-Strip. Seropositives were parasitologically examined, and their dried blood spots tested in trypanolysis, ELISA/Tbg, m18S-qPCR and LAMP. The HAT prevalence in the study population was calculated based on RDT positivity followed by parasitological confirmation. The association between clinical symptoms and signs and RDT positivity was determined using multivariable logistic regression. The tests' Positive Predictive Value (PPV), specificity and agreement were determined. Results Over 29 months, 3433 clinical suspects were tested. The RDT positivity rate was 2.83%, HAT prevalence 0.06%. Individuals with sleep disturbances (p<0.001), motor disorders (p = 0.002), convulsions (p = 0.02), severe weight loss (p = 0.02) or psychiatric problems (p = 0.04) had an increased odds (odds ratios 1.7-4.6) of being HAT RDT seropositive. Specificities ranged between 97.8%-99.6% for individual RDTs, and 93.3-98.9% for subsequent tests on dried blood spots. The PPV of the individual RDTs was below 14.3% (CI 2-43), increased to 33.3% (CI 4-78) for serial RDT combinations, and reached 67% for LAMP and ELISA/Tbg on RDT positives. Agreement between diagnostic tests was poor to moderate (Kappa [less than or equal to] 0.60), except for LAMP and ELISA/Tbg (Kappa = 0.66). Conclusion Identification of five key clinical symptoms and signs may simplify referral for HAT RDT screening. The results confirm the appropriateness of the diagnostic algorithm presently applied, with screening by SD Bioline HAT or HAT Sero-K-Set, supplemented with trypanolysis. ELISA/Tbg could replace trypanolysis and is simpler to perform. Trial registration ClinicalTrials.gov ClinicalTrials.gov, ID NCT03356665

Animal African trypanosomosis is an important vector-borne disease of livestock in sub-Saharan Africa. Pigs seem relatively tolerant to trypanosome infection and could act as a reservoir of trypanosomes affecting animals and humans. Our ability to reliably detect trypanosome infection in pigs depends on the performance of diagnostic tools, which is not well known. In pigs experimentally infected with Trypanosoma brucei brucei , we evaluated the performance of parasitological Buffy Coat Technique (BCT), two molecular (TBR and 5.8S PCR) and four serological tests (CATT, HAT Sero- K -Set rapid diagnostic test–RDT, indirect ELISA, immune trypanolysis). Most diagnostic tests showed high specificity, estimated at 100% (95% CI = 74–100%) with the exception of CATT and RDT whose specificity varied between 100% (95% CI = 74–100%) to 50% (95% CI = 7–93%) during the experiment. The sensitivity of each test fluctuated over the course of the infection. The percentage of positive BCT over the infection (30%) was lower than of positive PCR (56% and 62%, depending on primers). Among the serological tests, the percentage of positive tests was 97%, 96%, 86% and 84% for RDT, ELISA, immune trypanolysis and CATT, respectively. Fair agreement was observed between both molecular tests (κ = 0.36). Among the serological tests, the agreement between the ELISA and the RDT was substantial (κ = 0.65). Our results on the T . b . brucei infection model suggest that serological techniques are efficient in detecting the chronic phase of infection, PCR is able to detect positive samples several months after parasites inoculation while BCT becomes negative. BCT examination and RDT are useful to get a quick information in the field, and BCT can be used for treatment decision. ELISA appears most suited for epidemiological studies. The selection of diagnostic tests for trypanosomosis in pigs depends on the context, the objectives and the available resources.

Human African trypanosomiasis is a neglected tropical disease primarily caused by the extracellular parasite Trypanosoma brucei gambiense . To avoid elimination by the host, these parasites repeatedly replace their variant surface glycoprotein (VSG) coat. Trypanosoma brucei gambiense is the primary causative agent of human African trypanosomiasis (HAT), a vector-borne disease endemic to West and Central Africa. The extracellular parasite evades antibody recognition within the host bloodstream by altering its variant surface glycoprotein (VSG) coat through a process of antigenic variation. The serological tests that are widely used to screen for HAT use VSG as one of the target antigens. However, the VSGs expressed during human infection have not been characterized. Here, we use VSG sequencing (VSG-seq) to analyze the VSGs expressed in the blood of patients infected with T. b. gambiense and compared them to VSG expression in Trypanosoma brucei rhodesiense infections in humans as well as Trypanosoma brucei brucei infections in mice. The 44 VSGs expressed during T. b. gambiense infection revealed a striking bias toward expression of type B N termini (82% of detected VSGs). This bias is specific to T. b. gambiense , which is unique among T. brucei subspecies in its chronic clinical presentation and anthroponotic nature. The expressed T. b. gambiense VSGs also share very little similarity to sequences from 36 T. b. gambiense whole-genome sequencing data sets, particularly in areas of the VSG protein exposed to host antibodies, suggesting the antigen repertoire is under strong selective pressure to diversify. Overall, this work demonstrates new features of antigenic variation in T. brucei gambiense and highlights the importance of understanding VSG repertoires in nature. IMPORTANCE Human African trypanosomiasis is a neglected tropical disease primarily caused by the extracellular parasite Trypanosoma brucei gambiense . To avoid elimination by the host, these parasites repeatedly replace their variant surface glycoprotein (VSG) coat. Despite the important role of VSGs in prolonging infection, VSG expression during human infections is poorly understood. A better understanding of natural VSG gene expression dynamics can clarify the mechanisms that T. brucei uses to alter its VSG coat. We analyzed the expressed VSGs detected in the blood of patients with trypanosomiasis. Our findings indicate that there are features of antigenic variation unique to human-infective T. brucei subspecies and that natural VSG repertoires may vary more than previously expected.

Human African trypanosomiasis (HAT), or sleeping sickness, is a neglected tropical disease that is fatal if untreated, caused by Trypanosoma brucei gambiense and T. brucei rhodesiense. In its 2012 roadmap, WHO targeted HAT for elimination as a public health problem in 2020 and for zero transmission in 2030. Diagnosis of HAT is a multistep procedure comprising of clinical suspicion, confirmation, and stage determination. Suspects are identified on clinical signs and/or on screening for specific antibodies. Parasitological confirmation of suspects remains mandatory to avoid unnecessary toxic drug administration. The positive predictive value of the antibody detection tests is low. Simple parasite detection techniques, microscopic examination of lymph node aspirate, or stained thick blood films lack sensitivity, whereas in T. brucei gambiense patients, the number of blood trypanosomes may be very low. Parasite concentration techniques are therefore indispensable. Half a century ago, Sheila Lanham discovered a technique to separate trypanosomes from the blood of infected rodents, based on anion exchange chromatography with diethyl amino ethyl (DEAE) cellulose, a weak anion exchanger. Between pH 6-9, trypanosome surface is less negatively charged than that of blood cells. When blood is poured on top of a DEAE cellulose column, blood cells are retained, whereas parasites pass the column together with the elution buffer. The result is a pure suspension of trypanosomes that retain their morphology and infectivity. Because cell surface charges vary among trypanosome and mammal species, the optimal buffer pH and ionic strength conditions for different combinations of host and trypanosome species were established. Lanham's technique revolutionized the diagnosis of HAT. It is indispensable in the production of the Card Agglutination Test for Trypanosomiasis (CATT), the most used field test for screening in T. brucei gambiense HAT foci and essential to confirm the diagnosis in suspected people. Lumsden and colleagues developed the mini anion exchange centrifugation technique (mAECT). After adaptation for field conditions, its superior diagnostic and analytical sensitivity compared to another concentration technique was demonstrated. It was recommended as the most sensitive test for demonstrating trypanosomes in human blood. At the beginning of the 21st century, the mAECT was redesigned, allowing examination of a larger volume of blood, up to 0.35 ml with whole blood and up to 10 ml with buffy coat. The plastic collector tube in the new kit is also used for detection of trypanosomes in the cerebrospinal fluid. Unfortunately, mAECT also has some disadvantages, including its price, the need to centrifuge the collector tube, and the fact that it is manufactured on a noncommercial basis at only two research institutes. In conclusion, 50 years after Sheila Lanham's discovery, CATT and mAECT have become essential elements in the elimination of HAT.

Co-resistance against the first-line antibiotics ampicillin, chloramphenicol and trimethoprim/sulphamethoxazole or multidrug resistance (MDR) is common in non typhoid Salmonella (NTS). Use of alternative antibiotics, such as fluoroquinolones or third generation cephalosporins is threatened by increasing resistance, but remains poorly documented in Central-Africa. As part of a microbiological surveillance study in DR Congo, blood cultures were collected between 2007 and 2011. Isolated NTS were assessed for serotype and antimicrobial resistance including decreased ciprofloxacin susceptibility and extended-spectrum beta-lactamase (ESBL) production. In total, 233 NTS isolates (representing 23.6% of clinically significant organisms) were collected, mainly consisting of Salmonella Typhimurium (79%) and Salmonella Enteritidis (18%). The majority of NTS were isolated in the rainy season, and recovered from children ≤2 years old. MDR, decreased ciprofloxacin susceptibility, azithromycin and cefotaxime resistance were 80.7%, 4.3%, 3.0% and 2.1% respectively. ESBL production was noted in three (1.3%) isolates. Decreased ciprofloxacin susceptibility was associated with mutations in codon 87 of the gyrA gene, while ESBLs all belonged to the SHV-2a type. Presence of almost full MDR among NTS isolates from blood cultures in Central Africa was confirmed. Resistance to fluoroquinolones, azithromycin and third generation cephalosporins is still low, but emerging. Increased microbiological surveillance in DR Congo is crucial for adapted antibiotic therapy and the development of treatment guidelines.

Background Passive diagnosis of human African trypanosomiasis (HAT) at the health facility level is a major component of HAT control in Guinea. We examined which clinical signs and symptoms are associated with HAT, and assessed the performance of selected clinical presentations, of rapid diagnostic tests (RDT), and of reference laboratory tests on dried blood spots (DBS) for diagnosing HAT in Guinea. Method The study took place in 14 health facilities in Guinea, where 2345 clinical suspects were tested with RDTs (HAT Sero- K -Set, rHAT Sero-Strip, and SD Bioline HAT). Seropositives underwent parasitological examination (reference test) to confirm HAT and their DBS were tested in indirect enzyme-linked immunoassay (ELISA)/ Trypanosoma brucei gambiense , trypanolysis, Loopamp Trypanosoma brucei Detection kit (LAMP) and m18S quantitative PCR (qPCR). Multivariable regression analysis assessed association of clinical presentation with HAT. Sensitivity, specificity, positive and negative predictive values of key clinical presentations, of the RDTs and of the DBS tests for HAT diagnosis were determined. Results The HAT prevalence, as confirmed parasitologically, was 2.0% (48/2345, 95% CI: 1.5–2.7%). Odds ratios ( OR ) for HAT were increased for participants with swollen lymph nodes ( OR  = 96.7, 95% CI: 20.7–452.0), important weight loss ( OR  = 20.4, 95% CI : 7.05–58.9), severe itching ( OR  = 45.9, 95% CI : 7.3–288.7) or motor disorders ( OR  = 4.5, 95% CI : 0.89–22.5). Presence of at least one of these clinical presentations was 75.6% (95% CI : 73.8–77.4%) specific and 97.9% (95% CI : 88.9–99.9%) sensitive for HAT. HAT Sero- K -Set, rHAT Sero-Strip, and SD Bioline HAT were respectively 97.5% (95% CI : 96.8–98.1%), 99.4% (95% CI : 99.0–99.7%) and 97.9% (95% CI : 97.2–98.4%) specific, and 100% (95% CI : 92.5–100.0%), 59.6% (95% CI : 44.3–73.3%) and 93.8% (95% CI : 82.8–98.7%) sensitive for HAT. The RDT’s positive and negative predictive values ranged from 45.2–66.7% and 99.2–100% respectively. All DBS tests had specificities ≥ 92.9%. While LAMP and m18S qPCR sensitivities were below 50%, trypanolysis and ELISA/ T.b. gambiense had sensitivities of 85.3% (95% CI : 68.9–95.0%) and 67.6% (95% CI : 49.5–82.6%). Conclusions Presence of swollen lymph nodes, important weight loss, severe itching or motor disorders are simple but accurate clinical criteria for HAT referral in HAT endemic areas in Guinea. Diagnostic performances of HAT Sero- K -Set and SD Bioline HAT are sufficient for referring positives to microscopy. Trypanolysis on DBS may discriminate HAT patients from false RDT positives. Trial registration The trial was registered under NCT03356665 in clinicaltrials.gov (November 29, 2017, retrospectively registered https://clinicaltrials.gov/ct2/show/NCT03356665 ) Graphical Abstract